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The gastro-intestinal (GI) tract is a very important part of the human digestive system but remains largely inaccessible for unobtrusive monitoring. Ingestible electronic devices are a very interesting concept to address this need. This paper discusses the current state of ingestible electronic devices and explores the potential they hold to provide unprecedented insight by measuring several aspects of the complex bio-chemical processes that happen in the GI tract in real-time. This will require novel sensor technology capable of measuring relevant markers with adequate specificity and accuracy. In order to be able to scale this functionality down to a form factor of an easily digestible pill, ultra-low-power wireless interface electronics are needed. This paper discussed some of the challenges related to sensing, wireless communication and powering where innovation is needed to enable the next generation of ingestible electronic devices. Index Terms-Ingestible, gastro-intestinal, electro-chemical sensing, wireless powering, CMOS integrated circuitsPLACEHOLDER for submission date. N. Van Helleputte is with imec, Belgium