In most cases, initialization basically means the assignment of values at time t = 0 for membrane potential, gating states, and ionic concentrations at every spatial position in the model. A model is properly initialized when clicking on the Init & Run button produces exactly the same results, regardless of previous simulation history. Of course we assume that model parameters have not changed between runs, and that any random number generator has been re-initialized with the same seed so that it produces the same sequence of “random” numbers. Models described by kinetic schemes require that each of the reactant states be initialized to some concentration. If linear circuits are involved, initial values must be assigned to voltages across capacitors and the internal states of operational amplifiers. For networks and other models that use the event delivery system, initialization also includes specifying which events are in transit to their destinations at time 0 (i.e. events generated, at least conceptually, at t ≤ 0 for delivery at t ≥ 0).