This review identifies several important challenges in null model testing in ecology: 1) developing randomization algorithms that generate appropriate patterns for a specified null hypothesis; these randomization algorithms stake out a middle ground between formal Pearson–Neyman tests (which require a fully-specified null distribution) and specific process-based models (which require parameter values that cannot be easily and independently estimated); 2) developing metrics that specify a particular pattern in a matrix, but ideally exclude other, related patterns; 3) avoiding classification schemes based on idealized matrix patterns that may prove to be inconsistent or contradictory when tested with empirical matrices that do not have the idealized pattern; 4) testing the performance of proposed null models and metrics with artificial test matrices that contain specified levels of pattern and randomness; 5) moving beyond simple presence–absence matrices to incorporate species-level traits (such as abundance) and site-level traits (such as habitat suitability) into null model analysis; 6) creating null models that perform well with many sites, many species pairs, and varying degrees of spatial autocorrelation in species occurrence data. In spite of these challenges, the development and application of null models has continued to provide valuable insights in ecology, evolution, and biogeography for over 80 years.