The concept emerging from Professor David Barker’s seminal research on the developmental origins of later life disease has progressed in many directions since first published. One critical question is when during gestation might environment alter the developmental programme with such enduring consequences. Here, we review the growing consensus from clinical and animal research that the period around conception, embracing gamete maturation and early embryogenesis, might be the most vulnerable period. We focus on four types of environmental exposure shown to modify periconceptional reproduction and offspring development and health: maternal overnutrition and obesity; maternal undernutrition; paternal diet and health; and assisted reproductive technology. These conditions may act through diverse epigenetic, cellular and physiological mechanisms to alter gene expression and cellular signalling and function in the conceptus affecting offspring growth and metabolism and leading to increased risk for cardiometabolic and neurological disease in later life.