Nonsyndromic cleft lip with or without an associated cleft palate (NSCLP) is one of the most common birth defects affecting 135,000 babies worldwide each year. It causes severe facial dysmorphism and treatment requires a multifaceted team approach. While treatment modalities have improved, the costs to families and the health care resources are still enormous. The causes of NSCLP are multifactorial with both genetic and environmental factors. Progress is being made towards defining the genetic variation underpinning NSCLP by utilizing gene discovery techniques including genome wide linkage, association mapping and a candidate gene approaches. To date, approximately 20% of the genetic contributions to NSCLP have been assigned to a small number of genes. This chapter provides a review of recent progress in defining the genetic causes of NSCLP.