Abstract The Midlatitude Cirrus experiment (ML-CIRRUS) deployed the High Altitude and Long Range Research Aircraft (HALO) to obtain new insights into nucleation, life cycle, and climate impact of natural cirrus and aircraft-induced contrail cirrus. Direct observations of cirrus properties and their variability are still incomplete, currently limiting our understanding of the clouds’ impact on climate. Also, dynamical effects on clouds and feedbacks are not adequately represented in today’s weather prediction models. Here, we present the rationale, objectives, and selected scientific highlights of ML-CIRRUS using the G-550 aircraft of the German atmospheric science community. The first combined in situ–remote sensing cloud mission with HALO united state-of-the-art cloud probes, a lidar and novel ice residual, aerosol, trace gas, and radiation instrumentation. The aircraft observations were accompanied by remote sensing from satellite and ground and by numerical simulations. In spring 2014, HALO performed 16 flights above Europe with a focus on anthropogenic contrail cirrus and midlatitude cirrus induced by frontal systems including warm conveyor belts and other dynamical regimes (jet streams, mountain waves, and convection). Highlights from ML-CIRRUS include 1) new observations of microphysical and radiative cirrus properties and their variability in meteorological regimes typical for midlatitudes, 2) insights into occurrence of in situ–formed and lifted liquid-origin cirrus, 3) validation of cloud forecasts and satellite products, 4) assessment of contrail predictability, and 5) direct observations of contrail cirrus and their distinction from natural cirrus. Hence, ML-CIRRUS provides a comprehensive dataset on cirrus in the densely populated European midlatitudes with the scope to enhance our understanding of cirrus clouds and their role for climate and weather.