Renal cell carcinoma (RCC) is the most common type of renal cancer in adults. RCC is notoriously resistant to current therapies suggesting the need to improve our knowledge and create more effective therapies. The molecular genetic defects that occur in RCC are extensive and complex ranging from single DNA changes, to large chromosomal defects, to signature disruptions in the transcription of hundreds of genes. These changes are often shared within each histological RCC subtype, illustrating their significance to the disease phenotype. This review presents an overview of the genetic abnormalities that occur within the most common subtypes of RCC. We discuss the recent molecular findings that have advanced our understanding of the somatic architecture of renal tumors and their impact on disease therapeutics.