Marvel Comics started a storyline that changed the Spidey universe and now said storyline is coming to an end. The story "Brand New Day" found Peter Parker without Mary Jane after making a deal with Mephisto to save Aunt May's life after she took a sniper round meant for Parker. On the plus side the Marvel Universe had forgotten Peter Parker was Spider Man after the great Civil War debacle and he could get on with super hero shenanigans.
Brand New Day also brought along with it a new writing team to help keep a good continuity flow. A three times a month Amazing Spider-Man comic and some fun new villains and interesting takes on villains of the past.
The last storyline titled "Origin of the Species" will be issues #642 to #647.
In November writer Dan Slott will take over writing duties and Amazing Spider-Man will become bi-weekly instead, but will increase from 22 pages to 30 pages. So I guess everything works out. For some cool exclusive images from future stories check out IGN.