Abstract Aim Mountains and islands are both well known for their high endemism. To explain this similarity, parallels have been drawn between the insularity of “true islands” (land surrounded by water) and the isolation of habitats within mountains (so-called “mountain islands”). However, parallels rarely go much beyond the observation that mountaintops are isolated from one another, as are true islands. Here, we challenge the analogy between mountains and true islands by re-evaluating the literature, focusing on isolation (the prime mechanism underlying species endemism by restricting gene flow) from a dynamic perspective over space and time. Framework We base our conceptualization of “isolation” on the arguments that no biological system is completely isolated; instead, isolation has multiple spatial and temporal dimensions relating to biological and environmental processes. We distinguish four key dimensions of isolation: (a) environmental difference from surroundings; (b) geographical distance to equivalent environment [points (a) and (b) are combined as “snapshot isolation”]; (c) continuity of isolation in space and time; and (d) total time over which isolation has been present [points (c) and (d) are combined as “isolation history”]. We evaluate the importance of each dimension in different types of mountains and true islands, demonstrating that substantial differences exist in the nature of isolation between and within each type. In particular, different types differ in their initial isolation and in the dynamic trajectories they follow, with distinct phases of varying isolation that interact with species traits over time to form present-day patterns of endemism. Conclusions Our spatio-temporal definition of isolation suggests that the analogy between true islands and mountain islands masks important variation of isolation over long time-scales. Our understanding of endemism in isolated systems can be greatly enriched if the dynamic spatio-temporal dimensions of isolation enter models as explanatory variables and if these models account for the trajectories of the history of a system.