Focusing on the Chumash, we examine the potential impacts of Old World epidemic diseases on protohistoric peoples of the southern California coast. Our study indicates that: (1) coastal peoples would have been highly susceptible to Old World disease epidemics; (2) native contacts with several sixteenth and seventeenth century European maritime expeditions were extensive; and (3) Old World diseases also were closing in on protohistoric California from the Southwest, Mexico, and Baja California. There is little clear evidence that Old World diseases devastated California's coastal tribes in the protohistoric period, but archaeologists have invested little energy searching for such evidence. We propose three models of protohistoric disease impacts to be tested with archaeological data, examine some problems in identifying protohistoric archaeological components along the California coast, and outline some archaeological patterns that might be linked to disease epidemics and associated cultural changes.