The causes of retinoblastoma (RB) can now be described with considerable accuracy, although many details are still unclear. Understanding the genetic changes leading to RB has provided an awareness of general mechanisms of cancer development and progression, previously only suspected. From the basic understanding have come new diagnostic technologies that are now ready to be applied directly to RB patients and their families, and a rational approach, based on this understanding, will help us to develop new therapies that avoid the severe complications of conventional treatment.