The execution of a software application or pipeline using various combinations of parameters and inputs is a common task in bioinformatics. In the absence of a specialized tool to organize, streamline and formalize this process, scientists must write frequently complex scripts to perform these tasks. We present nestly, a Python package to facilitate running tools with nested combinations of parameters and inputs. nestly provides three components. First, a module to build nested directory structures corresponding to choices of parameters. Second, the nestrun script to run a given command using each set of parameter choices. Third, the nestagg script to aggregate results of the individual runs into a CSV file, as well as support for more complex aggregation. We also include a module for easily specifying nested dependencies for the SCons build tool, enabling incremental builds.