We have presented a formal, theoretically sound framework that provides reliable and accurate simulations of the diffusion-reaction process for biological systems. We compared it with the methods of Smoluchowski [22] and its extension by Andrews and Bray [17]. Figure 1 illustrates the different approaches compared in this study. The first case (A) is the original Smoluchowski approach. In this approach, at each short timestep δt in the diffusion process the distance between the chemical entities is checked and if they come into close proximity (distance d <σb) the two entities are said to have reacted together. The downside of the approach is that many diffusion steps need to be computed to simulate the reaction kinetics accurately. The second approach (B) is that of Andrews and Bray [17]. In their scheme, the reaction radius, σb, is adjusted so that the correct reaction kinetics are reproduced for timesteps Δt ≥ 100 × δt. This approach produces an efficient algorithm that yields the correct reaction kinetics while using larger timesteps. Finally, (C) illustrates the present approach where the reaction radius is replaced by a smooth interaction probability. The two entities are considered to diffuse freely during the timestep Δt thereby producing a probability PAB (d, Δt) of interaction.