Prader-Willi syndrome (PWS) is a complex disorder with a vast variable clinical presentation, resulting from the loss of paternally inherited genes on chromosome 15q11-q13. The loss of expression of one or more genes located within the PWS critical region results in the various phenotypes. PWS can occur via three different distinct genetic mechanisms including paternal deletion of the 15q11-q13, maternal uniparental disomy (mUPD), or imprinting defects. Although there are some clinical symptoms that are shared among PWS patients, the overall complexity of the syndrome results in unique clinical presentations, emphasizing the importance of genetic diagnosis and counseling, where individual based therapy can be implemented. DNA methylation status was first confirmed, followed by the identification of one of the three molecular mechanisms. Individuals who suffered from paternal deletions shared common symptoms like low birth weight, lower IQ, hypopigmentation and maladaptive behaviours. The type of PWS deletion (type I or II) also impacts the clinical presentation, with type I patients having a more severe presentation and acquiring speech later than those with type II. Individuals with mUPD tend to present with lower birth length, various sleep disorders, psychosis and Autism Spectrum Disorder (ASD). In addition, the average maternal age in the mUDP patients was higher than those with deletions. No single gene mutation has been shown to contribute to PWS or related to any exclusive symptoms. Although some genes like MKRN3, MAGEL2, NDN do not address the full spectrum of symptoms, others have noted that SNORD116 located within the SNURF-SNRPN complex has become a critical candidate for PWS due to its role in growth retardation and neuroendocrine disturbances leading to hyperphagia and obesity. The broad spectrum of PWS observed in patients and the absence of a clear genotype-phenotype relationship, implies that various genes involved, have an intensified effect on the various phenotypes when lost.