This paper presents an electrostatic discharge (ESD) protection circuit and reviews best practices to interface a CMOS analog-front end with off-chip high impedance (>10 GΩ) and high precision current (<0.1 pA resolution) sensors. The proposed circuit uses a buffer at the input/output (I/O) pin to drive the voltage across the ESD protection diodes to a near-zero value enabling leakage below 20 fA across the entire input range.