In the Smart Microscopy Lab we focus on understanding how to connect bioimage analysis with computer-controlled microscopy to generate automated and adaptive imaging workflows and to enable quantitative and statistically meaningful results in complex biological systems. This approach brings new challenges, such as performing real-time image processing, accessing and controlling instrument hardware via suitable software, designing efficient workflows, and handling large data sets during operation. The possibilities to combine different imaging technologies, to trigger imaging modalities based on the real-time image analysis results, and to synchronize image acquisition with external devices for sample manipulation (i.e., liquid handling or cell manipulation) enable the automation of complex workflows. Such workflows allow researchers to acquire images in a less biased, more reproducible, and faster way than manual imaging by means of experiments otherwise hardly feasible.