Metalloenzymes play essential roles in nearly all biological processes and as such represent a rich target space for drug development and biomanufacturing. This presentation will address many of the challenges faced by crystallographers studying metalloproteins, including verification of the correct incorporation and chemical state of the metal of interest, and maintenance of the optimal environment for data collection, including anaerobic, aphotic, controlled humidity and/or temperature. Further, the metal centers of metalloenzymes, especially those that are redox active, are very susceptible to X-ray induced photoreduction. Finally, many structural investigations of metalloproteins are transitioning beyond solving a single static structure, to the acquisition of sequential structural snapshots that provide details of the atomic positions and motions that define the relationships involved in molecular recognition, transition state stabilization, and other aspects of the biocatalytic process. Developments at SSRL and LCLS-MFX will be presented that tackle challenges involved in the study of metalloenzymes and the use of small and radiation-sensitive crystals, and to perform time-resolved crystallography. To facilitate the handling and optimization of delicate crystals, new in situ crystallization and remote data collection schemes have been released that avoid direct manipulation of crystals, support robotic sample exchange, and allow full rotational access of the sample in a controlled humidity environment. By simplifying crystal handling and transport at near-physiological temperatures, these technologies remove barriers to enable more widespread use of multi-temperature and serial crystallography methods to study metalloenzyme structure and protein dynamics. Strategies for time-resolved measurements and data analysis tools that provide rapid feedback for experimental optimization during fast-paced experiments will also be described.