Increasing indications, reports and studies demonstrate that threats from the deliberate use of chemical weapons remain high and are evolving. One of the deadliest classes of chemical weapons are the organophosphorus nerve agents. It is now clear that both state and non-state actors have the ability to deploy and use these types of weapons against individuals and the wider civilian population posing a real and significant threat. The objective of this article is to provide an overview of the issues impacting on a timely critical response to the accidental or deliberate release of Organophosphorus Nerve Agents in order to enhance the understanding of their effects and provide guidance on how first responders might better treat themselves or victims of exposure through a discussion of available evidence and best practices for rapid skin decontamination. The article also examines use of the current nomenclature of 'wet' and 'dry' to describe different forms of decontamination. One of the key conclusions of this article is that adequate preparedness is essential to ensuring that responders are trained to understand the threat posed by Organophosphorus Nerve Agents as well as how to approach a contaminated environment. A key aspect to achieving this will be to ensure that generic medical countermeasures are forward-deployed and available, preferably within minutes of a contamination and that first responders know how to use them.