Very frequent and extremely crude sexual jokes, and they are cruder with every season.
Charlie sleeps with some stranger(s) in almost every episode.
In a CSI type episode Charlie makes a joke saying, "How much trouble? Slap on the wrist trouble, or pack my things and tape my butt shut trouble." There is then a clip with Charlie in a jail cell with a very big man standing behind him. The man then says,"I like it when its gift wrapped." You then hear a tearing sound and Charlies face looks panicked, implying that the man ripped the tape off and is about to rape Charlie.
In the same CSI episode the groom (his new stepdad) is lying on Charlie's bed, dead, with his pants down implying he was having sex. The wife (Charlie's mom) then walks in and says she did not have sex with him so everyone realizes the man was cheating. There is repeated conversation about how he has lipstick on his dipstick. CSI then walks in and says that they are going to look for evidence. They then scan the room for semen samples. As you might have guessed, since it is Charlie's room and he has sex in there almost every night, there is semen everywhere. The semen is not seen, but there are quite a few jokes about it.
Charlie's long lost daughter, Jenny, is revealed to be a lesbian, she makes pretty graphic sexual references about women that she's had sex with
Frequent talk about sex, masturbation, porn, and other mature sexual subjects.
While some of the sex jokes are quite direct, the double entendres/innuendos will go over kids' heads.
Seasons 1 to 6 have a lot of mild sexual references.
Seasons 7 to 12 have way more frequent and graphic sexual references than the earlier ones.
There is an episode in Season 7 and the plot of the episode is that Charlie cannot give his girlfriend orgasms. Strong sexual references in this episode.
There is a season 7 episode where it is implied that a woman is performing oral sex on Alan.
In season 9 there are two episodes where Alan receives oral sex
Season 11 probably has the most graphic sexual references