Shake flasks are the most commonly used small-scale cultivation vessel for microbial fermentation and cell culture. Their ease-of use and low cost per experiment provide an ideal set-up for strain selection, yield optimization, and overall bioprocess characterization. Traditionally, shake flasks are black boxes. Available manual sampling methods rarely provide enough information to understand one’s bioprocess fully, are time-consuming, and come with additional risks. New, modern sensor technologies allow scientists to study key parameters in shake flasks non-invasively, automatically, and in real time, enabling bioreactor-like capabilities at the shake flask level.