The signal-to-noise ratio (SNR) for real-time biosensing with liquid-gated carbon nanotube transistors is crucial for exploring the limits of their sensitivity, but has not been studied thus far. Although biosensing is often performed at high transconductance where the device displays the largest gate response, here we show that the maximum SNR is actually obtained when the device is operated in the subthreshold regime. In the ON-state, additional contributions to the noise can lead to a reduction of the SNR by up to a factor of 5. For devices with passivated contact regions, the SNR in ON-state is even further reduced than for bare devices. We show that when the conductivity of the contact regions can be increased using a conventional back gate, the SNR in the ON-state can be improved. The results presented here demonstrate that biosensing experiments are best performed in the subthreshold regime for optimal SNR.