A key event in hypoxic pulmonary vasoconstriction (HPV) is the elevation in smooth muscle intracellular Ca2+ concentration. However, there is controversy concerning the source of this Ca2+, the signal transduction pathways involved, and the identity of the oxygen sensor. Although there is wide support for the hypothesis that hypoxia elicits depolarisation via inhibition of K+ channels, and thus promotes Ca2+ entry through L-type channels, a significant number of studies are inconsistent with this mechanism being either the sole or even major means by which Ca2+ is elevated during HPV. There is strong evidence that intracellular Ca2+ stores play a critical role, and voltage-independent Ca2+ entry mechanisms including capacitative Ca2+ entry (CCE) have also been implicated. There is renewed interest in the role of mitochondria in HPV, both in terms of modulators of Ca2+ homeostasis per se and as oxygen sensors. There is however considerable uncertainty concerning the mechanisms involved in the latter, with proposals for changes in redox couples and both an increase and decrease in mitochondrial production of reactive oxygen species (ROS). In this article we review the evidence for and against involvement of such mechanisms in HPV, and propose a model for the regulation of intracellular [Ca2+] in pulmonary artery during hypoxia in which the mitochondria play a central role.