Carbon nanotubes have been attracting a lot of interest as electron transfer mediators to enhance electrochemical biosensing. The main reason behind this is usually recognized in terms of augmented electrochemical active surface area. The aim of this paper is to review other phenomena that occur at the electrochemical interface. Three distinct features of these phenomena mainly appear in electrochemical biosensing. We introduce the Cottrell, Randle-Sevcick, and Nernst effects to address these features. By using these features, several electrochemical biosensing systems are investigated. Differences among the proposed systems are presented and analyzed in light of these effects. We finally have demonstrated that carbon nanotubes may induce completely opposite effects when dealing with different biosensing systems. This paper also shows that even seemingly small differences (e.g., changing metabolite as detected by the same enzyme) might result in opposite effects on the same carbon nanotube based sensor. Nevertheless, it is shown that carbon nanotubes, in some cases, confirm their exceptional nature in enhancing the sensor performance by orders of magnitude. The sensitivity increases from 87 +/- 62 to 3718 +/- 73 nA/mu M x cm(2) and detection limit decreases from 7.5 +/- 5.3 mM to 84 +/- 2 mu M in case of cyclophosphamide detected by the cytochromes P450 3A4. (C) 2014 Elsevier Ltd. All rights reserved.