During the past few decades, there have been major advances in our understanding of the human immune system and its associated lymphoproliferative disorders, including those involving the skin. These advances have been facilitated by the development of new genomic technologies that have led not only to more accurate classification and diagnosis of these diseases but also to fresh insights into their pathogenesis and improved means of staging disease, monitoring response to therapy, and detecting early relapse. Rather than exhaustively summarizing this field, the purpose of this review is to provide an overview of key advances, emphasizing their current and future relevance to general dermatologists. Most of the issues raised in this article are discussed and referenced in greater detail in a recent comprehensive textbook chapter.1