Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer’s disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR’s molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases. Although these advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer’s disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine (BBR) has been used as an over -the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR’s molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes. One of the advantages of BBR is its multiple-target effects in each of these diseases. Therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets ngle-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.