Patch clamp electrophysiology has transformed research in the life sciences over the last few decades. Since their
inception, automatic patch clamp platforms have evolved considerably, demonstrating the capability to address both
voltage and ligand gated channels, and showing the potential to play a pivotal role in drug discovery and biomedical
research. Unfortunately, the cell suspension assays to which early systems were limited cannot recreate biologically
relevant cellular environments, or capture higher-order aspects of synaptic physiology and network dynamics. In vivo
patch clamp electrophysiology has the potential to yield more biologically complex information and be especially useful
in reverse engineering the molecular and cellular mechanisms of single-cell and network neuronal computation, while
capturing important aspects of human disease mechanisms and possible therapeutic strategies. Unfortunately, it is
a difficult procedure with a steep learning curve, which has restricted dissemination of the technique. Luckily, In
vivo patch clamp electrophysiology seems particularly amenable to robotic automation. In this review, we document
the development of automated patch clamp technology, from early systems based on multi-well plates through to
automated planar array platforms, and modern robotic platforms capable of performing two-photon targeted whole-cell
electrophysiological recordings in vivo.