Asthma is a chronic inflammatory respiratory condition characterised by airway constriction, smooth muscle spasm, and severe morbidity. It affects around 300 million people globally, with children being especially vulnerable. Despite its worldwide effect, the invention of innovative asthma medicines has been slow over the last 5 decades, leaving significant unmet requirements in asthma care. Although intriguing medicines have demonstrated efficacy in animal models, many fail to fulfil safety and effectiveness requirements in human trials, highlighting the critical need for more predictive models that better transfer to human results. This comprehensive review investigates the mechanisms and efficacy of anti-asthmatic drugs using both genetic and conventional animal models. Both genetic and traditional models of anti-asthmatic agents, their characteristics, and their significance are summarized as: