Attention to safety is essential in any imaging facility. In the context of low- and middle-income countries, limited resources may complicate the attempt to set up and operate an imaging facility with the highest safety standards. However, all applicable safety measures must be nonetheless carried out. Imaging safety involves several general principles, including optimizing radiation exposure to be consistent with answering the clinical question at hand. Facilities must address safety considerations relevant to patients, staff, and the general public. Considerations specific to individual modalities include appropriate limitations on radiation exposure in X-ray and CT imaging, attention to magnetic field hazards in magnetic resonance imaging, proper preparation and control of radionuclides in nuclear medicine, and avoidance of unnecessary prenatal imaging procedures with ultrasound. An important general safety consideration for all imaging modalities is assuring proper clinical utilization, which includes factors such as not performing imaging procedures without medical referral and supervision, attention to image quality to ensure procedures are not repeated unnecessarily and reduce delayed or missed diagnoses, and carefully considering the clinical appropriateness of any requested imaging procedure. Facilities must also ensure equitable access to diagnostic imaging to maximize the benefit-to-risk ratio. Staff training and credentialing are of utmost importance and include staff who design, prepare, and evaluate a new imaging facility as well as medical staff who acquire, order, or review images. Ensuring imaging safety requires the input of a team of experts, including trained and qualified medical physicists, health physicists, radiation safety officers, clinical safety personnel, installation and service personnel, radiologic technologists, and physicians. With appropriate attention to safety, diagnostic imaging is an essential component of healthcare services in resource-limited regions.