Malaria caused by the protozoan parasite Plasmodium falciparum is characterized by long-term, persistent infections that can last for many months. The ability of this parasite to avoid clearance by the human immune system is dependent on its capacity to continuously alter the surface exposed antigenic proteins that that are vulnerable to antibody recognition and attack, a process called antigenic variation. Significant work in recent years has contributed to our understanding of the mechanisms underlying this process, including the genes encoding the antigenic proteins and the DNA sequence elements that control their expression. In addition, the epigenetic "marks" that are associated with activation and silencing of individual genes have been extensively characterized. These studies have led to a model that includes multiple layers of regulation that ultimately lead to the tight coordination of expression of the genes responsible for antigenic variation by malaria parasites. Here we review some more recent data that adds additional complexity to our understanding of these regulatory layers.