Recent work has demonstrated single-electron sensitivity in carbon nanotube transistors under a variety of conditions, including room temperature. In noncovalent cases like charged adsorbates or SiO₂ imperfections, two-level fluctuators near the nanotube perturb the current electrostatically. In other cases, a sidewall defect or other covalent modification directly on the nanotube sidewall sensitizes a particular site. Comparative research has helped reveal differences in the transduction mechanisms of the two cases and provides design rules for maximizing reliable signals for electronic sensing. For example, noncovalent sensitization generally produces a smaller signal amplitude in a background of low-energy fluctuators at varying distances from the nanotube. Covalent modifications are far more sensitive than noncovalent perturbations, but the new degrees of freedom that accompany covalent disorder often have energy scales similar to the signal of interest, leading to multiple independent fluctuations that degrade the overall signal-to-noise for sensing. An outstanding compromise involves short, noncovalent linkers, which can produce highly predictable signal amplitudes without degradation of the device characteristics. Furthermore, noncovalent fabrication methods are scalable, so that wafer-scale arrays of molecular sensors are most likely to follow this path.