The analysis of the early development of self-injurious behavior (SIB) has, to date, reflected the wider distinction between nature and nurture. Despite the status of genetic factors as risk markers for the later development of SIB, a model that accounts for their influence on early behavior-environment relations is lacking. In the current paper we argue that the investigation of gene-environment interactions (GxE) and other forms of gene-environment interplay could potentially enhance current approaches to the study of self-injury. A conceptual model of the early development of SIB based explicitly on such relations is presented. The model is consistent with the basic tenets of functional analysis. Implications for research and the assessment, treatment, and prevention of SIB are discussed.