Understanding the response of Neotropical vegetation to environmental variability is integral to understanding how tropical biomes will react to ongoing climate changes. The last 50,000 years provide a natural ecophysiological experiment for studying plant population responses, with global and regional fluctuations in temperature, precipitation, and carbon dioxide. The response patterns of tropical vegetation reflect the adaptive potential of these taxa in the face of climate change, past and present. This is a preliminary investigation of Neotropical Holocene vegetation response to climatic variability using a multivariate analytical approach. This statistical look at vegetation dynamics uses over 80 published South American pollen records and correlates patterns of taxonomic association with trends in available independent climate proxy data. The results potentially highlight the degree of susceptibility of a number of tropical genera and families to water, temperature, and carbon dioxide stress. A parallel analysis of 154 South and Meso-American forest transects provides generalized insights on the modern distribution of Neotropical families and genera and the environmental conditions that may govern these distributions.