Methamphetamine (METH, or ice) use is a global burden, which continues to pervade and plague contemporary society with estimates of up to 35 million users worldwide. METH is a psychotropic compound which acts on the central nervous system, and, in chronic doses, can induce psychotic behavior from its highly addictive nature. METH harbours the capacity to cause modulation of immune cells, enabling the drug to have lasting, long-term effects which may manifest into neuropsychiatric disorders, as well as leading to increased susceptibility to communicable diseases, such as HIV. In addition, changes to the cytokine balance have been associated with blood brain barrier compromise, resulting to alterations to brain plasticity, creating lasting neurotoxicity. Furthermore, immune-related signaling pathways are key to further evaluating how METH impacts the host immunity through these neurological and peripheral modifications. Layering this knowledge with current data on inflammatory responses can help facilitate a better understanding of how the host adaptive and innate immunity responds to METH, how this can activate premature-ageing processes and how METH exacerbates disturbances leading to non-communicable age-related diseases, including cardiovascular disease, stroke, depression and dementia.