Cryptococcus neoformans and Cryptococcus gattii comprise the pathogenic Cryptococcus species complex. This chapter focuses on the population structure and ecology of C. neoformans and C. gattii. It summarizes the current knowledge of the population structure of C. neoformans and C. gattii and discusses the associations of the genetically isolated subpopulations with their ecological niches. The most reliable methods developed to genotype individuals use markers that detect polymorphisms among microsatellites and similar repetitive DNA elements, restriction fragment length polymorphisms (RFLP), amplified fragment length polymorphisms (AFLP), and direct DNA sequencing, such as multilocus sequence typing (MLST). Most studies of the population genetics of the pathogenic species of Cryptococcus use reference strains to recognize the major clades or subpopulations. These are designated as VNI through VNIV and VNB for C. neoformans and VGI through VGIV for C. gattii. A table shows the current designation of the nine major subpopulations of the C. neoformans/C. gattii complex and their relationships to the conventional serotypes. This method of serotyping served for years to separate C. neoformans (serotypes A, D, and AD) from C. gattii (serotypes B and C). Analyses of the population structure presented in the chapter are concerned with (i) genetic diversity, (ii) mode of reproduction (clonality versus recombination), and (iii) population subdivision. The chapter also talks about the advances in the understanding of the intertwining effects of ecology and genetics on the lifestyle of C. neoformans and C. gattii.