The main topic of Ghettoside is the issue of black-on-black violence—homicide in particular, but also the myriad other forms of violence that take place, including, e.g., almocide, a term used to describe shootings and other violence that nearly kill the victim, but do not. (The man in the wheelchair who provided key information, for example, had been paralyzed in a seemingly arbitrary shooting.) Leovy presents this topic as one that is simultaneously understood and misunderstood, in that the public and law enforcement are aware of the problem, yet largely uninterested in uncovering the roots of the problem or taking steps to solve it. The media, for example, rarely reports on shootings in South Central, and even when it does, the reports are strikingly at odds with the real events. For example, late in the book, a 13-year-old shooting victim who had been wearing an absurdly-outdated orange bandana was described as essentially a hardcore gang member in the news report. Law enforcement, likewise, is largely unconcerned by the violence, choosing to believe that in ghettoside violence, there are no real victims, and that violence is just part of black culture.

Leovy attacks this from multiple angles. Her thesis can be understood more simply as that black-on-black violence is not only a problem that can be solved, but must be solved for both humanitarian and practical reasons.