Loneliness has been associated with different health outcomes in the following domains: general health, well-being, physical health, mental health, sleep, and cognitive function. However, the most significant associations fall into mental health- and well-being-related outcomes. Moreover, loneliness is an identified risk factor for all-cause mortality. This article overviews the systematic and meta-analytic studies, which have investigated epidemiology and etiology, associated medical and neuropsychiatric conditions, and interventions for loneliness. Meta-analyses have associated higher levels/prevalence of loneliness with pathological conditions, including physical (cardiovascular diseases, obesity, and cancer) and mental health conditions (dementia, cognitive impairment, depression, anxiety, suicide, substance abuse, frailty, and addiction). Furthermore, loneliness commonly occurs to people during particular physiological conditions, for example, childhood, adulthood, elderly, pregnancy, and taking care of others. Moreover, young adults commonly experience transient loneliness. For all these pathological/physiological conditions, COVID-19 has been confirmed as a loneliness-worsening condition. Genetic background, in addition to environmental factors, plays a role in the etiology of loneliness. Biomarkers mainly include neural correlates, including aberrations in the structure/function of cognitive or emotional control-related brain regions, inflammatory correlates, and anthropometric measures. The current interventions for loneliness alleviation are mostly focused on older people, for whom the evidence derived from systematic or meta-analytic studies shows none-to-moderate benefits and substantial heterogeneity across studies. The evidence is not adequate to conclude about the effectiveness of interventions in youth. In addition to the need for pathology- and population-specific interventions for loneliness reduction/prevention, there is a need to survey loneliness longitudinally to examine the causality of loneliness-health associations.