No, it wasn't about marijuana legalization, as he jokes in his opening statement, but an issue that he called even more important: awareness about Alzheimer's disease.
At 55 years old, his mother-in-law Adele Miller was diagnosed with early on-set Alzheimer's. By 60, she forgot how to speak, go to the bathroom on her own and dress herself.
He said before Miller was diagnosed with the disease, he had no idea those were possible symptoms, thinking rather that it had to do with forgotten keys, wearing mis-matched shoes, and asking the same questions over and over again.
He spoke of the shame and stigma attached to the disease that he said grows out of a lack of hope, which he said was his motivation to start an organization called Hilarity for Charity.
"That's right, the situation is so dire, that it caused me, a lazy, self-involved, generally self-medicated man-child, to start an entire charity organization," he said.
He urged the government for more help for Alzheimer's disease patients, stressing that he couldn't figure out how people with more limited income than his own could deal with the treatment.
But he also wanted to show people they're not alone.
"So few people share their personal stories. So few people have something to relate to," he said. "I know if me and my wife saw someone like me talking about this, it would probably make us feel a little less alone."
Watch Rogen's full, heartfelt address below.