Habitat loss and fragmentation are among the largest threats to amphibian populations. However, most studies have not provided clear insights into their population-level implications. There is a critical need to investigate the mechanisms that underlie patterns of distribution and abundance. In order to understand the population- and species-level implications of habitat loss and fragmentation, it is necessary to move from site-specific inferences to assessments of how the influences of multiple factors interact across extensive landscapes to influence population size and population connectivity. The goal of this paper is to summarize the state of knowledge, identify information gaps and suggest research approaches to provide reliable knowledge and effective conservation of amphibians in landscapes experiencing habitat loss and fragmentation. Reliable inferences require attention to species-specific ecological characteristics and their interactions with environmental conditions at a range of spatial scales. Habitat connectivity appears to play a key role in regional viability of amphibian populations. In amphibians, population connectivity is predominantly effected through juvenile dispersal. The preponderance of evidence suggests that the short-term impact of habitat loss and fragmentation increases with dispersal ability. However, species with limited dispersal abilities are likely to be equally imperiled by habitat loss and fragmentation over longer time periods. Rigorous understanding of the effects of habitat loss and fragmentation on amphibians will require species-specific, multi-scale, mechanistic investigations, and will be benefit from integrating large empirical field studies with molecular genetics and simulation modeling. Molecular genetic methods are particularly suited to quantifying the influences of habitat structure across large spatial extents on gene flow and population connectivity. Conservation strategies would benefit by moving from generalizations to species and process specific recommendations and by moving from site-specific actions to implementing conservation plans at multiple scales across broad landscapes.