SUMMARY Pathogens must acquire essential nutrients to successfully colonize and proliferate in host tissue. Additionally, nutrients provide signals that condition pathogen deployment of factors that promote disease. A series of transcriptomics experiments over the last 20 years, primarily with Cryptococcus neoformans and to a lesser extent with Cryptococcus gattii , provide insights into the nutritional requirements for proliferation in host tissues. Notably, the identified functions include a number of transporters for key nutrients including sugars, amino acids, metals, and phosphate. Here, we first summarize the in vivo gene expression studies and then discuss the follow-up analyses that specifically test the relevance of the identified transporters for the ability of the pathogens to cause disease. The conclusion is that predictions based on transcriptional profiling of cryptococcal cells in infected tissue are well supported by subsequent investigations using targeted mutations. Overall, the combination of transcriptomic and genetic approaches provides substantial insights into the nutritional requirements that underpin proliferation in the host.