Alkenone-based proxies are routinely used for paleoceanographic and climatologic reconstructions despite the fact that their calibration to environmental parameters is still a matter of debate. Significant differences are observed among culture calibrations using different strains of alkenone producers, between regional field calibrations within the euphotic zone and, between water column- and coretop-based calibrations. The reasons for these discrepancies are not well understood and call for further evaluation. Herein the possibility is raised that several aspects of genetics, physiology and ecology of alkenone-producing haptophytes may be responsible and suggestions of future research are proposed.