Some 30 years ago, one of us (CPP) proposed that platelets were involved in multiple processes physiologically, and in numerous pathophysiological conditions, beyond their well-established role in haemostasis and thrombosis (Page, Trends Pharmacol Sci 9(2): 66–71, 1988). In addition, it was proposed that there must be a dichotomy of platelet activation contributing to these different functions beyond what was understood about the role of platelets in haemostasis and thrombosis. In particular there is now considerable evidence that platelets participate in a number of inflammatory diseases, both in their own right and by facilitating leukocyte recruitment. In addition to the physiological counterpart to inflammation is host defence, and there is now increasing evidence for a critical role for platelets in protection against infections. The involvement of platelets in both host defence and inflammation involves mechanisms distinct from those involved with platelet activation in haemostasis and thrombosis. Here we review the current evidence that platelets play a role in host defence and allergic and non-allergic inflammation, and the implications these findings have for the development of future treatments for a range of inflammatory diseases.