Guatemala's major diplomatic interests are regional security and, increasingly, regional development and economic integration. The Central American Ministers of Trade meet on a regular basis to work on regional approaches to trade issues. In March 1998, Guatemala joined its Central American neighbors in signing a Trade and Investment Framework Agreement (TIFA). In 2000 it joined Honduras and El Salvador in signing a free trade agreement with Mexico, which went into effect in 2001. Guatemala also originated the idea for, and is the seat of, the Central American Parliament (PARLACEN).

Guatemala participates in several regional groups, particularly those related to the environment and trade. For example, US President Clinton and the Central American presidents signed the CONCAUSA (Conjunto Centroamerica-USA ) agreement at the Summit of the Americas in December 1994. CONCAUSA is a cooperative plan of action to promote clean, efficient energy use; conserve the region's biodiversity; strengthen legal and institutional frameworks and compliance mechanisms; and improve and harmonize environmental protection standards.

Guatemala has a longstanding claim to a large portion of Belize; the territorial dispute caused problems with the United Kingdom and later with Belize following its 1981 independence from the U.K. In December 1989, Guatemala sponsored Belize for permanent observer status in the Organization of American States (OAS). In September 1991, Guatemala recognized Belize's independence and established diplomatic ties, while acknowledging that the boundaries remained in dispute. In anticipation of an effort to bring the border dispute to an end in early 1996, the Guatemalan Congress ratified two long-pending international agreements governing frontier issues and maritime rights.

In early 2000, the Guatemalan Foreign Ministry proposed a border settlement that would transfer more than half of Belize's territory to Guatemala. Following a spate of border incidents, both sides agreed during talks under OAS auspices in November 2000 to confidence-building measures to reduce tensions. They followed that with an agreement on opening substantive discussions on the dispute.

Guatemala maintains official relations with the Republic of China (known as "Taiwan") instead of the People's Republic of China.

Disputes - international: territory in Belize claimed by Guatemala; precise alignment of boundary in dispute

Illicit drugs: transit country for cocaine shipments; minor producer of illicit opium poppy and cannabis for the international drug trade; active eradication program in 1996 effectively eliminated the cannabis crop; proximity to Mexico makes Guatemala a major staging area for drugs (cocaine shipments)