Used in combination with (heavily) modified Simple Colorbox plugin.

conditional-simple-colorbox.php

<?php
if ( class_exists( 'Simple_Colorbox' ) ) :
/**
 * Conditional Simple Colorbox loader.
 *
 * Enqueue Colorbox files only when needed on page to improve
 * performance by avoiding unnecessary external requests and
 * inline content.
 *
 * If Colorbox is needed only when galleries are used,
 * remove expensive search through post's content. 
 */
class Conditional_Simple_Colorbox extends Simple_Colorbox {
	/**
	 * Adds all the methods to appropriate hooks or shortcodes.
	 */
	public function __construct() {
		// Load parent
		parent::__construct();

		// Remove action hooks
		remove_action( 'wp_enqueue_scripts', array( $this, 'external_css'     ) );
		remove_action( 'wp_enqueue_scripts', array( $this, 'external_scripts' ) );

		// Add filter
		add_filter( 'the_content',  array( $this, 'the_content'  ) );
		add_filter( 'post_gallery', array( $this, 'post_gallery' ) );
	}

	/**
	 * Load Colorbox when there is a link to image in post's content.
	 *
	 * @todo Improve REGEX to find only links without img tags.
	 */
	public function the_content( $content ) {
		if ( ! did_action( 'md_loaded_colorbox' ) ) {
			$num = preg_match_all( '#(http://[^\s]+(?=\.(jpe?g|png|gif)))#i', $content, $matches );
			if ( $num > 0 ) {
				$this->external_css();
				$this->external_scripts();
				do_action( 'md_loaded_colorbox' );
			}
		}

		return $content;
	}

	/**
	 * Load Colorbox on gallery shortcode.
	 */
	public function post_gallery( $output ) {
		if ( ! did_action( 'md_loaded_colorbox' ) ) {
			$this->external_css();
			$this->external_scripts();
			do_action( 'md_loaded_colorbox' );
		}

		return $output;
	}
}

/**
 * Initialize Colorbox.
 *
 * Load class when all plugins are loaded
 * so that other plugins can overwrite it.
 */
function conditional_simple_colorbox_instantiate() {
	global $simple_colorbox;
	$simple_colorbox = new Conditional_Simple_Colorbox();
}
add_action( 'plugins_loaded', 'conditional_simple_colorbox_instantiate', 15 );

/**
 * Deinitialize a Simple Colorbox plugin.
 *
 * Unload class when all plugins are loaded
 * but before class in instantiated.
 */
function conditional_simple_colorbox_deinstantiate() {
	remove_action( 'plugins_loaded', 'simple_colorbox_instantiate', 15 );
}
add_action( 'plugins_loaded', 'conditional_simple_colorbox_deinstantiate', 14 );
endif; // class_exists( 'Simple_Colorbox' )