The scientific understanding of disease causation was crucial to the ways in which the Spanish colonial state addressed epidemic diseases which periodically struck nineteenth-century Philippines. Scholars have often described Spanish colonial responses in terms of ineptitude and failure, and have often glossed over the multiple and competing scientific theories that preoccupied Spanish and Filipino physicians. This article examines the work and ideas of nineteenth-century Spanish colonial and patriotic Filipino physicians regarding disease causation in the tropical environment of the Philippines. It will focus on two key developments—Spanish environmentalist thinking and the emerging fields of microscopy and bacteriology. Much like the British and French colonialists, Spaniards viewed tropical climates as insalubrious and conducive to disease, perceiving themselves as constitutionally at risk in hot places, ill-suited, exposed, and vulnerable to so-called native diseases. By the 1880s, however, young Filipino researchers, some of whom had trained in Spain and France, were undertaking new research on polluted water, malaria, and cells. Influenced by the revolutionary new discoveries being made in bacteriology, these researchers questioned prevailing environmentalist explanations and focused, for the first time, on the nature of pathogens and microbial pathogenesis in disease development and transmission. But germ theory remained an idea among many. This article argues that although late nineteenth-century studies in microscopy by Filipinos slowly began to challenge Spanish colonial ideas, different streams of thinking overlapped and no single scientific explanation came to predominate.