The holistic principles of hygiene and public health have contributed substantially to an increase in life expectancy by more than 30 years and in life quality since the beginning of the 20th century. Frank, Pettenkofer, Nightingale, Pasteur, Lister, and Koch have been pioneering protagonists of the holistic approach to hygiene and public health. Socioeconomic development and related factors such as nutrition status and food hygiene, housing conditions, water supply and sewage systems, and education (including motivation for personal hygiene) have obviously been of more importance for life expectancy and life quality than progress in curative medicine, such as availability of microbial diagnosis, vaccination, and antibiotics. Today, new risk factors for infectious diseases arise, even in developed countries. These risk factors arise from emerging pathogens, antibiotic-resistant microorganisms, changing demographic patterns, an increasing amount of ambulatory and home care, socioeconomic and environmental changes, technical environments, worldwide distribution of food, and changing human behavior with a decreased awareness of microbial threats. These new challenges worldwide make a renewal of the holistic approach of hygiene and public health both urgent and necessary. On the basis of historic experience, policies that focus on surveillance and control, diagnosis, and therapy only can be assumed to be both insufficient and inefficient in controlling the new challenges in infectious diseases. Experiences in Germany with a holistic hospital hygiene strategy since 1976 provide encouragement for the promotion of holistic health concepts. Risk assessment, risk management, and risk communication are basic steps of a modern holistic strategy. Hygiene has the potential to act as a moderator of diverging positions of different disciplines within this renewed approach.