The GEneral NEural SImulation System (GENESIS) is an open source simulation platform for realistic modeling of systems ranging from subcellular components and biochemical reactions to detailed models of single neurons, simulations of large networks of realistic neurons, and systems-level models. The graphical interface XODUS permits the construction of a wide variety of interfaces for the control and visualization of simulations. The object-oriented scripting language allows one to easily construct and modify simulations built from the GENESIS libraries of simulation components. Here, we present procedures for installing GENESIS and its supplementary tutorials, running GENESIS simulations, and creating new neural simulations.