The impact of mold growth in homes located on First Nations reserves in Canada is part of a national housing crisis that has not been adequately studied. Nearly half of the homes on reserves contain mold at levels of contamination associated with high rates of respiratory and other illnesses to residents. Mold thrives due to increased moisture levels in building envelopes and interior spaces. Increased moisture stems from several deficiencies in housing conditions, including structural damage to the building envelope, overcrowding and insufficient use of ventilation systems, and other moisture-control strategies. These deficiencies have developed due to a series of historical and socioeconomic factors, including disenfranchisement from traditional territory, environmentally inappropriate construction, high unemployment rates, lack of home ownership, and insufficient federal funding for on-reserve housing and socioeconomic improvements. The successful, long-term reduction of mold growth requires increased activity in several research and policy areas. First, the actual impacts on health need to be studied and associated with comprehensive experimental data on mold growth to understand the unique environmental conditions that permit the germination and growth of toxic mold species. Second, field data documenting the extent of mold growth in on-reserve homes do not exist but are essential in understanding the full extent of the crisis. Third, current government initiatives to educate homeowners in mold remediation and prevention techniques must be long lasting and effective. Finally, and most importantly, the federal government must make a renewed and lasting commitment to improve the socioeconomic conditions on reserves that perpetuate mold growth in homes. Without such improvement, the mold crisis will surely persist and likely worsen.