Candida albicans is an important opportunistic fungal pathogen of humans. Phenotypic plasticity is a typical biological feature of C. albicans, which is associated with pathogenicity, host adaptation, and sexual reproduction. Biofilm of C. albicans is a complex community formed by different morphological types of cells (yeast, hyphae and pseudohyphae) and secreted extracellular matrix. C. albicans biofilms are intrinsically resistant to antifungal drugs, the host immune system, and environmental stresses. Biofilm is an important virulence factor and a major clinical challenge. With the development of new technologies in global gene expression profiles and genetic manipulation, the regulatory mechanisms that govern C. albicans biofilm development and drug resistance become more and more clear. Major regulatory mechanisms involve the MAPK and cAMP signaling pathways and transcriptional regulators such as Bcr1 and Tec1. In addition, morphological transitions and sexual reproduction are also involved in the regulation of biofilm development. In this review, we focus on the genetic regulatory mechanisms of biofilm including the roles of cell-wall related proteins, transcription factors, and the MTL locus. In the last section, we also summarize the mechanisms of drug resistance of biofilm in C. albicans.