Drug abuse imposes costs on individuals and society. Researchers have produced several studies on a subset of tangible costs of drug abuse and other illnesses, but key tangible costs sometimes have been overlooked and, even when recognized, rarely have been estimated. An assortment of intangible costs also have received very little research attention. This study outlines a comprehensive conceptual framework for estimating the social cost of drug abuse. We address both the tangible and intangible costs for the drug-abusing and non-drug-abusing population. Our conceptual framework is based on critical reviews of new and traditional methods for estimating the costs of illness and disease including cost-of-illness methods, averting behavior methods, and utility valuation techniques. We show how the proposed methods can be combined with existing data to estimate the total social cost of drug abuse. Using social cost estimates will enable policymakers to more accurately assess the total burden of drug abuse and related problems on society.