Coccidioidomycosis, also known as valley fever, is an infection caused by inhalation of Coccidioides spp. spores. This soil-dwelling fungus is endemic to arid regions of Mexico, Central and South America, and the southwestern United States. Symptomatic patients typically experience a self-limited influenza-like illness, but some develop severe or chronic pulmonary disease, and less than 1% of patients experience disseminated disease. Coccidioidomycosis can be costly and debilitating, with nearly 75% of patients missing work or school because of their illness, and more than 40% requiring hospitalization. Previous publications have reported state-specific increases in coccidioidomycosis in Arizona and California during 1998-2001 and 2000-2007, respectively. To characterize long-term national trends, CDC analyzed data from the National Notifiable Diseases Surveillance System (NNDSS) for the period 1998-2011. This report describes the results of that analysis, which indicated that the incidence of reported coccidioidomycosis increased substantially during this period, from 5.3 per 100,000 population in the endemic area (Arizona, California, Nevada, New Mexico, and Utah) in 1998 to 42.6 per 100,000 in 2011. Health-care providers should be aware of this increasingly common infection when treating persons with influenza-like illness or pneumonia who live in or have traveled to endemic areas.