Although the genetic study of Candida albicans is generally less convenient than that of Saccharomyces cerevisiae, recent advances in the molecular genetics of C. albicans have greatly facilitated the study of this important human fungal pathogen. This chapter discusses the development of a novel strategy for large-scale synthetic genetic analysis in C. albicans based on complex haploin-sufficiency (CHI). An actin null mutant (act1?) containing ACT1 on a plasmid was mated to the set of single-gene-deletion strains and then cured of the plasmid to give a set of complex heterozygotes (act1Δ/ACT1 yfgΔ/YFG). Many of the genes identified using this genetic approach demonstrated defects in the actin cytoskeleton, confirming the ability of CHI to identify interacting pairs of genes and genes with similar cellular functions. The development of a large-scale synthetic genetic screen using CHI to understand the role of the RAM network in C. albicans morphological transition is described. As new mutagenesis techniques are developed and as large collections of mutants are created, it is likely that the creative application of these principles to genetic interaction analysis will lead to a deeper understanding of the complex regulatory networks that orchestrate C. albicans biology and pathogenesis.