The segment consists of eleven pressurized components and various external elements, almost all of which were delivered by the Space Shuttle.

On the forward end of Harmony is PMA-2, which was used by visiting Space Shuttles as a mating adapter and by future crewed missions to the ISS.

[6] The Destiny lab is managed by mission control centers in Houston, Texas and Huntsville, Alabama.

[7] It is host to scientific research in fluids, biology, medicine, materials and Earth sciences.

The module is unique in that it has a small airlock, which can be used to pass payloads to the robotic arms or astronauts outside the station.

The equipment lock is where the Extravehicular Mobility Units are stored and preparations for spacewalks are carried out.

Originally the Multi-Purpose Logistics Module (MPLM) Leonardo, it was converted to stay on orbit for an extended period of time prior to being installed on the ISS.

[5] The Pressurized Mating Adapters (PMA) serve as docking ports on the USOS portion of the ISS.

It converts the standard Common Berthing Mechanism to APAS-95, the docking system that was used by the Space Shuttle and the Russian Orbital Segment.

The truss system itself consists of 12 total segments—four on each side, and one central segment—which are connected to the ISS by attachment points on the Destiny module.

[19] The thirteenth piece, known as the Zenith-1 (Z1) truss segment, is attached to the Unity module, and was originally used to hold the P6 solar arrays to provide power to the USOS.

The Z1 segment now houses the Ku-band antennas and serves as a routing point for power and data cables on the exterior of the ISS.

The Integrated Truss Structure also houses the main cooling system for the ISS, which consists of two pumps, two radiator arrays, and two ammonia and two nitrogen tank assemblies.

External Stowage Platform 1 is located on the port side of the Destiny lab and was delivered on the STS-102 mission in March 2001.

[27] The ExPRESS logistics carriers (ELCs) are similar to the External Stowage Platform, but designed to carry more cargo.

[34] The Alpha Magnetic Spectrometer (AMS) is a particle physics experiment that is mounted on the S3 truss segment.

Once these cables are connected, the Canadarm2 will be able to position itself on the exterior of Zarya and will be able to support Extra-vehicular Activity (EVA) in the vicinity the Russian Orbital Segment (ROS).

[36] The Special Purpose Dexterous Manipulator (SPDM), also known as Dextre, is a two armed robot that can be attached to the ISS, the Mobile Base System or Canadarm2.

These tasks include switching orbital replacement units or moving ORUs from their stowage locations to where they are to be installed.

[10] The Mobile Base System (MBS) is a rail car-like device installed on the Integrated Truss Structure of the ISS.

The MBS also has a common attach system, to grapple a special capture bar on payloads.

It also has its own main computer and video distribution units, and remote power control modules.

[39] The Enhanced ISS Boom Assembly is used to extend the reach of Canadarm2 and provides detailed inspection capability.

The boom is also fitted with handrails, so that it can assist spacewalkers during EVAs as was done on STS-120 to repair the solar arrays.

[40] As of December 2024[update], Axiom Space expects to launch one module to the ISS, where it will dock at one of two ports currently used by cargo spacecraft.

If produced, this centrifuge would have been the first in-space demonstration of sufficient scale for artificial partial-G effects.

[46][47] Operational control of the US Orbital Segment of the ISS is accomplished by NASA and the ESA, the agency that manages the civilian portion of the US government space program.

[51] In 2010, NASA began to open up a limited amount of its space and astronaut time on the US Orbital Segment to commercial use.

In 2005, the US Congress authorized that one of the several U.S. National Laboratories should exist on board the ISS, and commercial research could be done there.

Prices to be paid by commercial companies utilizing the ISS National Lab on USOS were heavily subsidized from 2010 until early 2021.