Following the outbreak of poliovirus in the countries in the Horn of Africa, Somalia, Kenya and Ethiopia, in two WHO regions, an outbreak response involving the WHO Africa and WHO East and Mediterranean Regions and partner agencies like the UNICEF in East and Southern African was developed. This paper documents response to polio virus outbreak in the Horn of Africa and the lessons learnt for the interregional and inter-agency collaboration on the response. This collaboration led to speedy interruption of the outbreak and within a period of one year the total virus load of 217 in 2013 was brought down to mere six. This resulted from collaborative planning and implementation of activities to boost the hitherto low immunity in the countries andimprove surveillance among others. A number of lesson were generated from the process. Some of the lessons is critical role such collaboration plays in ensuring simultaneous immunity boosting, information and resources sharing, among other. Some challenges were equally encountered, chiefly in the appropriation of authorities. In conclusion, however, one is safe to note that the collaboration was very fruitful given the timely interruption of transmission.