It is a topic of interest to me, and as always I find that Dopers’ tastes and recommendations are second to none.
I’m familiar with Clean and Sober, Rush, and The Days of Wine and Roses.
Sir Rhosis
The Lost Weekend comes to mind.
I’ve always felt that Harold & Khumar Go To White Castle hit a little too close to home.
The underrated When a Man Loves a Woman.
Trainspotting? (I’m asking, not telling.)
The Panic in Needle Park
Born to Win
Drugstore Cowboy
Reefer Madness: The Musical 
OK, seriously, what about Blow? I don’t know much about drugs, so I don’t really know how accurate the portrayals are.
Yes. I’m not a heroin addict, but opiate addiction of any kind is pretty nasty to get over. For me, the movie depicted a more extreme version of withdrawal than I had experienced from the “legal” opiates.
On the lighter side, 28 Days made me chuckle with recognition a few times. When the heroin addict was eating sweets (common with opiate withdrawal, IME) and when Sandra Bullock’s character had a moment of morality and threw her pills out the window, then fell out of the window when she tried to get them back. The meetings were also amusing because I recognized a lot of the characters.
And Leaving Las Vegas.
Not a film, but the HBO series The Corner is a realistic, hard-hitting look at the effects of drug abuse from multiple perspectives.
What about Requiem For A Dream?
I only have vague memories of it, but I wonder if LESS THAN ZERO counts as realistic.
Any thoughts on this?
True Blue Jack
I’ve never been able to watch all of The Bad Lieutenant
(not sure if this meets your criteria, but…)
David Janssen starred in a really gritty TV movie about the effects of alcoholism on an aeronautical engineer in “A Sensitive, Passionate Man.”
Love, Liza is a woefully underdistributed film in which Philip Seymour Hoffman plays a young professional who turns to solvent abuse when he can’t deal with his wife’s suicide.
It’s a truly fantastic film, but it’s fecking heartwrenching. Best performance Hoffman has turned in so far (although I haven’t seen Capote yet.)
I would hazard that “Less Than Zero” was realistic in that the worst hardcore drug addict dies in the end, even though he had decided to quit - there was no happy ending for him. It is also extremely realistic in the sense that the hardcore drug addict was Robert Downey, Jr. 
I haven’t seen “My Private Idaho,” but there is a rumour that River Phoenix developed his drug addiction during this movie (also that Keanu did too, but that is even more unsubstantiated.)
I should point out that while his character abuses substances, he isn’t a substance abuser. (Watch it with the commentary for more info.)
Under the Volcano is a fantastic film about a day in the life of an alcoholic. Sad, but well done.
Jeez, featherlou, if you’re going to mention Keanu and Robert Downey Jr., I’m going to have to give next year’s A Scanner Darkly an advance nod.
It’s not strictly realistic, being set in the undefined future and describing a fantasy drug called “Substance D” or “Death,” but as far as realistic depictions of drug abuse are concerned, it’s right on the money. It’s actually a roman à clef that Philip K. Dick wrote about his descent into paranoid delusion during years of heavy methamphetamine use, and his observation of all the people in his scene who went nuts or died. He’d have episodes of dissociative behaviour where he’d tear his house apart (in one instance blowing open his own safe with explosives,) not remember any of it, and spend huge amounts of time worrying about the vast conspiracy of agents working against him.
The book was written in 1977, but with the huge increase in meth use in the past decade or so, A Scanner Darkly is more topical than ever – and it’s an incredibly intimate study of tweaker psychology and behaviour.
tdn, my copy of Love, Liza is unfortunately VHS – so no commentary for me. Can you elaborate on that? Do you mean that he’s not a substance abuser in the sense that he’s not really interested in drinking or using the usual drugs of abuse, but just kind of accidentally fell into huffing?
I should have put more thought into my OP. Specifically, I’m thinking more along the lines of “Alcohol/substance abuse’s effect on a family unit/interpersonal relationships/romances, etc.”
Any of those films fit that criteria?
Sir Rhosis