Asthma is a complex disorder which has increased dramatically in prevalence over the past three decades. Current therapies, based on the T helper type 2 (Th2) paradigm, have not been able to control this disease. Epidemiological studies have demonstrated an association between infection with the hepatitis A virus (HAV) and protection against the development of asthma, and genetic studies have shown that the HAV receptor, TIM-1 (T cell, immunoglobulin domain and mucin domain), is an important atopy susceptibility gene. Furthermore, recent studies indicate that TIM-1 is a receptor for phosphatidylserine, an important marker of apoptotic cells. These studies together suggest that HAV and TIM-1 may potently regulate asthma through novel non-Th2-mediated mechanisms. Further study of the immunobiology of TIM-1 and its involvement in the clearance of apoptotic cells is likely to provide important insight into the mechanisms that lead to, and those that protect against, asthma, and how infection affects immunity and the development of asthma.