This work analyzes the patch-clamp technique, which is the gold standard for ion channel measurements in electrophysiology, as well as the required instrumentation and main interferences that may affect the measurement accuracy. Different sources of degradation are evaluated, such as failure in headstage cooling and pipette/electrode impedance compensation systems, electromagnetic interference (EMI) coupling from environmental wireless signals, and noise coupling from power supplies and/or the peristaltic pump motor. Robotized patch-clamp measurement systems are also considered. Experimental evaluation of the possible effects on patch-clamp metrological performance and some countermeasures to mitigate them are discussed. Daily recordings are presented to show the effects of interferences on ion channel drug analysis.