This review aims to provide a comprehensive overview of the in vitro, animal, and clinical studies with the bacterial strain Lactiplantibacillus plantarum 299v (L. plantarum 299v; formerly named Lactobacillus plantarum 299v) published up until June 30, 2020. L. plantarum 299v is the most documented L. plantarum strain in the world, described in over 170 scientific publications out of which more than 60 are human clinical studies. The genome sequence of L. plantarum 299v has been determined and is available in the public domain (GenBank Accession number: NZ_LEAV01000004). The probiotic strain L. plantarum 299v was isolated from healthy human intestinal mucosa three decades ago by scientists at Lund University, Sweden. Thirty years later, a wealth of data coming from in vitro, animal, and clinical studies exist, showing benefits primarily for gastrointestinal health, such as reduced flatulence and abdominal pain in patients with irritable bowel syndrome (IBS). Moreover, several clinical studies have shown positive effects of L. plantarum 299v on iron absorption and more recently also on iron status. L. plantarum 299v is safe for human consumption and does not confer antibiotic resistance. It survives the harsh conditions of the human gastrointestinal tract, adheres to mannose residues on the intestinal epithelial cells and has in some cases been re-isolated more than ten days after administration ceased. Besides studying health benefits, research groups around the globe have investigated L. plantarum 299v in a range of applications and processes. L. plantarum 299v is used in many different food applications as well as in various dietary supplements. In a freeze-dried format, L. plantarum 299v is robust and stable at room temperature, enabling long shelf-lives of consumer healthcare products such as capsules, tablets, or powder sachets. The strain is patent protected for a wide range of indications and applications worldwide as well as trademarked as LP299V®.