Critical civil infrastructure systems such as bridges, high rises, dams, nuclear power plants and pipelines present a major investment and the health of the United States' economy and the lifestyle of its citizens both depend on their safety and security. The challenge for engineers is to maintain the safety and security of these large structures in the face of terrorism threats, natural disasters and long-term deterioration, as well as to meet the demands of emergency response times. With the significant negative impact that these threats can have on the structural environment, health monitoring of civil infrastructure holds promise as a way to provide information for near real-time condition assessment of the structure's safety and security. This information can be used to assess the integrity of the structure for post-earthquake and terrorist attacks rescue and recovery, and to safely and rapidly remove the debris and to temporary shore specific structural elements. This information can also be used for identification of incipient damage in structures experiencing long-term deterioration. However, one of the major obstacles preventing sensor-based monitoring is the lack of reliable, easy-to-install, cost-effective and harsh environment resistant sensors that can be densely embedded into large-scale civil infrastructure systems. Nanotechnology and MEMS-based systems which have matured in recent years represent an innovative solution to current damage detection systems, leading to wireless, inexpensive, durable, compact, and high-density information collection. In this paper, ongoing research activities at Alabama A&M University (AAMU) Center for Transportation Infrastructure Safety and Security on the application of nanotechnology and MEMS to Civil Infrastructure for health monitoring will presented. To date, research showed that nanotechnology and MEMS-based systems can be used to wirelessly detect and monitor different damage mechanisms in concrete structures as well as monitor critical structures' stability during floods and barge impact. However, some technical issues that needs to be addressed before full implementation of these new systems and will also be discussed in this paper.