Individuals with Down Syndrome (DS) are commonly characterized by unique neurocognitive and neurobehavioural profiles that emerge within specific stages in the developmental continuum. A plethora of studies have confirmed DS's relationship to premature aging and subsequent cognitive decline. Due to having three copies of the amyloid precursor protein (APP) gene which results in amyloid-beta plaque deposition, the cognitive decline often resembles the decline observed in Alzheimer's disease. More specifically, as individuals with DS mature in age (>40) they experience a dramatic increase in difficulties in several cognitive domains, such as language, visuo-spatial abilities, executive functions, working memory, etc. Especially, frontal functions are reported to show an inverse correlation with age. In contrast to the pronounced and well-described neuropsychological deficits, psychiatric symptoms presented by this patient category are not uniform. Mental health disturbances commonly include general anxiety, obsessive-compulsive or oppositional/aggressive behaviors, depression and sleep disorders, as well as self-injury and behavior belonging to autistic spectrum disorders. Therefore, the purpose of the present review is twofold. Our first goal is to depict the cognitive and behavioural phenotype of adults with DS and our second goal is to review the current treatment options available for the behavioral and psychological symptoms, with an emphasis put on the quality of evidence available through meta-analyses and appraising critically the anecdotal treatment often applied. We also present a review on the psychotropic medication, especially acetylcholinesterase inhibitors, that can potentially slow the progression of cognitive decline of those patients. Finally, novel therapeutic strategies, psychological interventions and future diagnostic and therapeutic challenges are discussed.