Cryptococcus neoformans and Cryptococcus gattii are World Health Organization critical and medium priority pathogens, respectively. These mainly impact people with human immunodeficiency virus residing in low- and middle-income countries, but other patient groups and settings are also affected. The high global morbidity and mortality and the limitations of current treatments provided an impetus for the development of a target product profile (TPP) for new anti-cryptococcal agents. Key attributes of the TPP include improved safety, superior (or at least comparable) activity to current treatments against all syndromes across the full disease spectrum (cryptococcal meningitis, cryptococcal pneumonia, etc.), relevance for C. neoformans and C. gattii , suitability for all age groups, oral and intravenous formulations, an acceptable treatment regimen, minimal/manageable drug-drug interactions, thermostability, and a barrier to resistance at least as high as current options. The aim of this TPP, along with the suggested discovery and development paths, is to assist all stakeholders in the development of novel cryptococcal disease treatments.