Exposure to molds can cause human disease through several well-defined mechanisms. In addition, many new mold-related illnesses have been hypothesized in recent years that remain largely or completely unproved. Concerns about mold exposure and its effects are so common that all health care providers, particularly allergists and immunologists, are frequently faced with issues regarding these real and asserted mold-related illnesses. The purpose of this position paper is to provide a state-of-the-art review of the role that molds are known to play in human disease, including asthma, allergic rhinitis, allergic bronchopulmonary aspergillosis, sinusitis, and hypersensitivity pneumonitis. In addition, other purported mold-related illnesses and the data that currently exist to support them are carefully reviewed, as are the currently available approaches for the evaluation of both patients and the environment.